Patients’ perceptions on non‐specific effects of acupuncture: Qualitative comparison between responders and non‐responders

Background: Non-specific effect of acupuncture constitutes part of the overall effect generated via clinical encounter beyond needle insertion and stimulation. It is unclear how responders and non-responders of acupuncture experience non-specific effects differently. We aimed to compare their experiences in a nested qualitative study embedded in an acupuncture randomized trial on functional dyspepsia. Methods: Purposive sampling was used to capture experience of responders (n=15) and non-responders (n=15) to acupuncture via individual in-depth interviews. Design and analysis followed a framework analysis approach, with reference to an existing model on acupuncture non-specific effects. Themes emerging outside of this model were purposefully explored. Results: Responders had a more trusting relationship with acupuncturist in response to their expression of empathy. In turn they were more actively engaged in lifestyle modifications and dietary advice offered by acupuncturists. Non-responders were not satisfied with the level of reassurance regarding acupuncture safety. They were also expecting more peer support from fellow participants, regarded that as an empowerment process for initiating and sustaining lifestyle changes. Conclusions: Our results highlighted key differences in acupuncture non-specific effect components experienced by responders and non-responders. Positive non-specific effects contributing to overall benefits could be enhanced by emphasizing on empathy expression from acupuncturists, trust-building, offering appropriate explanations on safety, and organizing patient support groups. Further research on the relative importance of each component is warranted

The trainees' perspective on developing an end-of-grant knowledge translation plan

<p>Abstract</p> <p>Background</p> <p>Knowledge translation (KT) is a rapidly growing field that is becoming an integral part of research protocols.</p> <p>Methods</p> <p>This meeting report describes one group's experience at the 2009 KT Canada Summer Institute in developing an end-of-grant KT plan for a randomized control trial proposal.</p> <p>Results</p> <p>Included is a discussion of the process, challenges, and recommendations from the trainee's perspective in developing an end-of-grant KT plan.</p> <p>Conclusion</p> <p>New researchers should consider developing an end-of-grant KT plan with strategies that move beyond passive dissemination to incorporate innovative means of collaboration with the end user to craft the message, package the information, and share the research findings with end users.</p

T Cell Receptor-Like Recognition of Tumor In Vivo by Synthetic Antibody Fragment

A major difficulty in treating cancer is the inability to differentiate between normal and tumor cells. The immune system differentiates tumor from normal cells by T cell receptor (TCR) binding of tumor-associated peptides bound to Major Histocompatibility Complex (pMHC) molecules. The peptides, derived from the tumor-specific proteins, are presented by MHC proteins, which then serve as cancer markers. The TCR is a difficult protein to use as a recombinant protein because of production issues and has poor affinity for pMHC; therefore, it is not a good choice for use as a tumor identifier outside of the immune system. We constructed a synthetic antibody-fragment (Fab) library in the phage-display format and isolated antibody-fragments that bind pMHC with high affinity and specificity. One Fab, fE75, recognizes our model cancer marker, the Human Epidermal growth factor Receptor 2 (HER2/neu) peptide, E75, bound to the MHC called Human Leukocyte Antigen-A2 (HLA-A2), with nanomolar affinity. The fE75 bound selectively to E75/HLA-A2 positive cancer cell lines in vitro. The fE75 Fab conjugated with 64Cu selectively accumulated in E75/HLA-A2 positive tumors and not in E75/HLA-A2 negative tumors in an HLA-A2 transgenic mouse as probed using positron emission tomography/computed tomography (PET/CT) imaging. Considering that hundreds to thousands of different peptides bound to HLA-A2 are present on the surface of each cell, the fact that fE75 arrives at the tumor at all shows extraordinary specificity. These antibody fragments have great potential for diagnosis and targeted drug delivery in cancer

Does prenatal micronutrient supplementation improve children's mental development? A systematic review

<p>Abstract</p> <p>Background</p> <p>Although maternal nutrient status influences all aspects of fetal development including the brain, the impact of micronutrient supplementation on the baby's mental function is a topic of debate. This systematic review assesses the effect of single and multiple micronutrient supplementation during pregnancy on offspring mental development.</p> <p>Methods</p> <p>Eleven electronic literature databases were searched using key terms of various combinations and filter string terms. Reference lists of articles selected for review were scanned for citations fitting the same inclusion criteria. Each stage of the literature retrieval and review process was conducted independently by two reviewers. The CONSORT checklist was used to assess study quality.</p> <p>Results</p> <p>A total of 1316 articles were retrieved from the electronic database search, of which 18 met the inclusion criteria and were evaluated. The selected studies were randomized controlled trials published from 1983 to 2010, with high variance in sample size, intervention type, and outcome measures. The median CONSORT score was 15 (range 12 - 19). Due to inconsistent interventions and outcome measures among the studies, no conclusive evidence was found that enhancing the intrauterine environment through micronutrient supplementation was associated with child mental development in a number of dimensions. There was some evidence to support n-3 fatty acids or multi-micronutrients having some positive effect on mental development, but the evidence for single nutrients was much weaker.</p> <p>Conclusions</p> <p>The study of children's mental outcomes as a function of prenatal supplementation is still relatively new, but the results of this systematic review suggest that further work with multiple micronutrients and/or n-3 fatty acids should be conducted.</p

What Works to Improve and Manage Fecal Incontinence in Care Home Residents Living With Dementia? A Realist Synthesis of the Evidence.

The prevalence of fecal incontinence (FI) in care homes is estimated to range from 30% to 50%. There is limited evidence of what is effective in the reduction and management of FI in care homes. Using realist synthesis, 6 potential program theories of what should work were identified. These addressed clinician-led support, assessment, and review; the contribution of teaching and support for care home staff on how to reduce and manage FI; addressing the causes and prevention of constipation; how cognitive and physical capacity of the resident affects outcomes; how the potential for recovery, reduction, and management of FI is understood by those involved; and how the care of people living with dementia and FI is integral to the work patterns of the care home and its staff. Dementia was a known risk factor for fecal incontinence (FI), but how it affected uptake of different interventions or the dementia specific continence and toileting skills staff require, were not addressed in the literature. There was a lack of dementia-specific evidence on continence aids. Most care home residents with FI will be doubly incontinent; there is, therefore, limited value in focusing solely on FI or single causes, such as constipation. Medical and nursing support for continence care is an important resource, but it is unhelpful to create a distinction between what is continence care and what is personal or intimate care. Prompted toileting is an approach that may be particularly beneficial for some residents. Valuing the intimate and personal care work unqualified and junior staff provide to people living with dementia and reinforcement of good practice in ways that are meaningful to this workforce are important clinician-led activities. Providing dementia-sensitive continence care within the daily work routines of care homes is key to helping to reduce and manage FI for this population

Cross-Sectional Study Protocol for the COVID-19 Impact Survey of Mothers and Their 7–11 Year Old Children in Alberta, Canada

Objectives: Our aim is to understand the effect of the COVID-19 pandemic on families who have been followed longitudinally in two cohorts studied in Alberta, Canada. We will examine household infections during the COVID-19 pandemic, financial impact, domestic violence, substance use, child school and daily life and relationships in the home. We will identify risk and protective factors for maternal mental health outcomes using longitudinal data that can inform policy and government resource allocation in future disasters.Methods: Mothers who are currently participating in two longitudinal studies, Alberta Pregnancy Outcomes and Nutrition (APrON; N = 1,800) and All Our Families (AOF: N = 2,534) were eligible to participate. Mothers were invited to complete the baseline COVID-19 Impact Survey (20–30 min) within 4 months of March 15, 2020, which was when the province of Alberta, Canada, implemented school closures and physical-distancing measures to prevent the spread of COVID-19. Mothers were asked to report on their own, their child's and their family's functioning. Mothers were re-surveyed at 6 months after completion of the initial COVID-19 Impact Survey, and will be re-surveyed again at 12 months.Results: Responses from participants in both cohorts will be examined in harmonized analyses as well as separately. Descriptive, multivariable analysis will be undertaken to examine risk and resiliency over time and factors that predict mental health and well-being.Conclusions: This study will provide timely information on the impact of COVID-19 for Albertan families. It will identify risk and protective factors for mental health and well-being among contemporary urban families supported by a publicly funded health care system to inform allocation of resources to support those most vulnerable during a global pandemic

Visualizing variation within global pneumococcal sequence clusters (GPSCS) and country population snapshots to contextualize pneumococcal isolates

Knowledge of pneumococcal lineages, their geographic distribution and antibiotic resistance patterns, can give insights into global pneumococcal disease. We provide interactive bioinformatic outputs to explore such topics, aiming to increase dissemi-nation of genomic insights to the wider community, without the need for specialist training. We prepared 12 country-specific phylogenetic snapshots, and international phylogenetic snapshots of 73 common Global Pneumococcal Sequence Clusters (GPSCs) previously defined using PopPUNK, and present them in Microreact. Gene presence and absence defined using Roary, and recombination profiles derived from Gubbins are presented in Phandango for each GPSC. Temporal phylogenetic signal was assessed for each GPSC using BactDating. We provide examples of how such resources can be used. In our example use of a country-specific phylogenetic snapshot we determined that serotype 14 was observed in nine unrelated genetic backgrounds in South Africa. The international phylogenetic snapshot of GPSC9, in which most serotype 14 isolates from South Africa were observed, highlights that there were three independent sub-clusters represented by South African serotype 14 isolates. We estimated from the GPSC9-dated tree that the sub-clusters were each established in South Africa during the 1980s. We show how recombination plots allowed the identification of a 20 kb recombination spanning the capsular polysaccharide locus within GPSC97. This was consistent with a switch from serotype 6A to 19A estimated to have occured in the 1990s from the GPSC97-dated tree. Plots of gene presence/absence of resistance genes (tet, erm, cat) across the GPSC23 phylogeny were consistent with acquisition of a composite transposon. We estimated from the GPSC23-dated tree that the acquisition occurred between 1953 and 1975. Finally, we demonstrate the assignment of GPSC31 to 17 externally generated pneumococcal serotype 1 assemblies from Utah via Pathogenwatch. Most of the Utah isolates clustered within GPSC31 in a USA-specific clade with the most recent common ancestor estimated between 1958 and 1981. The resources we have provided can be used to explore to data, test hypothesis and generate new hypotheses. The accessible assignment of GPSCs allows others to contextualize their own collections beyond the data presented here.Fil: Gladstone, Rebecca A.. Wellcome Sanger Institute; Reino UnidoFil: Lo, Stephanie W.. Wellcome Sanger Institute; Reino UnidoFil: Goater, Richard. Wellcome Sanger Institute; Reino Unido. University of Oxford; Reino UnidoFil: Yeats, Corin. Wellcome Sanger Institute; Reino Unido. University of Oxford; Reino UnidoFil: Taylor, Ben. Wellcome Sanger Institute; Reino Unido. University of Oxford; Reino UnidoFil: Hadfield, James. Fred Hutchinson Cancer Research Center; Estados UnidosFil: Lees, John A.. Imperial College London; Reino UnidoFil: Croucher, Nicholas J.. Imperial College London; Reino UnidoFil: van Tonder, Andries. Wellcome Sanger Institute; Reino Unido. University of Cambridge; Estados UnidosFil: Bentley, Leon J.. Wellcome Sanger Institute; Reino UnidoFil: Quah, Fu Xiang. Wellcome Sanger Institute; Reino UnidoFil: Blaschke, Anne J.. University of Utah; Estados UnidosFil: Pershing, Nicole L.. University of Utah; Estados UnidosFil: Byington, Carrie L.. University of California; Estados UnidosFil: Balaji, Veeraraghavan. Christian Medical College; IndiaFil: Hryniewicz, Waleria. National Medicines Institute; PoloniaFil: Sigauque, Betuel. Instituto Nacional de Saude Maputo; MozambiqueFil: Ravikumar, K. L.. Kempegowda Institute Of Medical Sciences; IndiaFil: Grassi Almeida, Samanta Cristine. Adolfo Lutz Institute; BrasilFil: Ochoa, Theresa J.. Universidad Peruana Cayetano Heredia; PerúFil: Ho, Pak Leung. The University Of Hong Kong; Hong KongFil: du Plessis, Mignon. National Institute for Communicable Diseases; SudáfricaFil: Ndlangisa, Kedibone M.. National Institute for Communicable Diseases; SudáfricaFil: Cornick, Jennifer. Malawi liverpool wellcome Trust Clinical Research Programme; MalauiFil: Kwambana Adams, Brenda. Colegio Universitario de Londres; Reino Unido. Medical Research Council Unit The Gambia at The London School of Hygiene & Tropical Medicine; GambiaFil: Benisty, Rachel. Ben Gurion University of the Negev; IsraelFil: Nzenze, Susan A.. University of the Witwatersrand; SudáfricaFil: Madhi, Shabir A.. University of the Witwatersrand; SudáfricaFil: Hawkins, Paulina A.. Emory University; Estados UnidosFil: Faccone, Diego Francisco. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas. Área de Antimicrobianos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Pneumococcal lineages associated with serotype replacement and antibiotic resistance in childhood invasive pneumococcal disease in the post-PCV13 era: an international whole-genome sequencing study

Background: Invasive pneumococcal disease remains an important health priority owing to increasing disease incidence caused by pneumococci expressing non-vaccine serotypes. We previously defined 621 Global Pneumococcal Sequence Clusters (GPSCs) by analysing 20 027 pneumococcal isolates collected worldwide and from previously published genomic data. In this study, we aimed to investigate the pneumococcal lineages behind the predominant serotypes, the mechanism of serotype replacement in disease, as well as the major pneumococcal lineages contributing to invasive pneumococcal disease in the post-vaccine era and their antibiotic resistant traits. Methods: We whole-genome sequenced 3233 invasive pneumococcal disease isolates from laboratory-based surveillance programmes in Hong Kong (n=78), Israel (n=701), Malawi (n=226), South Africa (n=1351), The Gambia (n=203), and the USA (n=674). The genomes represented pneumococci from before and after pneumococcal conjugate vaccine (PCV) introductions and were from children younger than 3 years. We identified predominant serotypes by prevalence and their major contributing lineages in each country, and assessed any serotype replacement by comparing the incidence rate between the pre-PCV and PCV periods for Israel, South Africa, and the USA. We defined the status of a lineage as vaccine-type GPSC (≥50% 13-valent PCV [PCV13] serotypes) or non-vaccine-type GPSC (>50% non-PCV13 serotypes) on the basis of its initial serotype composition detected in the earliest vaccine period to measure their individual contribution toward serotype replacement in each country. Major pneumococcal lineages in the PCV period were identified by pooled incidence rate using a random effects model. Findings: The five most prevalent serotypes in the PCV13 period varied between countries, with only serotypes 5, 12F, 15B/C, 19A, 33F, and 35B/D common to two or more countries. The five most prevalent serotypes in the PCV13 period varied between countries, with only serotypes 5, 12F, 15B/C, 19A, 33F, and 35B/D common to two or more countries. These serotypes were associated with more than one lineage, except for serotype 5 (GPSC8). Serotype replacement was mainly mediated by expansion of non-vaccine serotypes within vaccine-type GPSCs and, to a lesser extent, by increases in non-vaccine-type GPSCs. A globally spreading lineage, GPSC3, expressing invasive serotypes 8 in South Africa and 33F in the USA and Israel, was the most common lineage causing non-vaccine serotype invasive pneumococcal disease in the PCV13 period. We observed that same prevalent non-vaccine serotypes could be associated with distinctive lineages in different countries, which exhibited dissimilar antibiotic resistance profiles. In non-vaccine serotype isolates, we detected significant increases in the prevalence of resistance to penicillin (52 [21%] of 249 vs 169 [29%] of 575, p=0·0016) and erythromycin (three [1%] of 249 vs 65 [11%] of 575, p=0·0031) in the PCV13 period compared with the pre-PCV period. Interpretation: Globally spreading lineages expressing invasive serotypes have an important role in serotype replacement, and emerging non-vaccine serotypes associated with different pneumococcal lineages in different countries might be explained by local antibiotic-selective pressures. Continued genomic surveillance of the dynamics of the pneumococcal population with increased geographical representation in the post-vaccine period will generate further knowledge for optimising future vaccine design. Funding: Bill & Melinda Gates Foundation, Wellcome Sanger Institute, and the US Centers for Disease Control.Fil: Lo, Stephanie W.. Wellcome Sanger Institute; Reino UnidoFil: Gladstone, Rebecca A.. Wellcome Sanger Institute; Reino UnidoFil: van Tonder, Andries J.. Wellcome Sanger Institute; Reino UnidoFil: Lees, John A.. University Of New York. School Of Medicine; Estados UnidosFil: du Plessis, Mignon. National Institute For Communicable Diseases; SudáfricaFil: Benisty, Rachel. Ben Gurion University of the Negev; IsraelFil: Givon Lavi, Noga. Ben Gurion University of the Negev; IsraelFil: Hawkins, Paulina A.. University of Emory. Rollins School of Public Health; Estados UnidosFil: Cornick, Jennifer E.. Malawi liverpool wellcome trust; MalauiFil: Kwambana Adams, Brenda. University College London; Estados UnidosFil: Law, Pierra Y.. University of Hong Kong; ChinaFil: Ho, Pak Leung. University of Hong Kong; ChinaFil: Antonio, Martin. Medical Research Council Unit The Gambia; GambiaFil: Everett, Dean B.. University of Edinburgh; Reino UnidoFil: Dagan, Ron. Ben Gurion University of the Negev; IsraelFil: Von Gottberg, Anne. National Institute For Communicable Diseases; SudáfricaFil: Klugman, Keith P.. University of Emory. Rollins School of Public Health; Estados UnidosFil: McGee, Lesley. Centers for Disease Control and Prevention; Estados UnidosFil: Breiman, Robert F.. University of Emory. Rollins School of Public Health; Estados UnidosFil: Bentley, Stephen D.. Wellcome Sanger Institute; Reino UnidoFil: Brooks, Abdullah W.. The Global Pneumococcal Sequencing Consortium; Reino UnidoFil: Corso, Alejandra. The Global Pneumococcal Sequencing Consortium; Reino Unido. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas. Área de Antimicrobianos; ArgentinaFil: Davydov, Alexander. The Global Pneumococcal Sequencing Consortium; Reino UnidoFil: Maguire, Alison. The Global Pneumococcal Sequencing Consortium; Reino UnidoFil: Pollard, Andrew. The Global Pneumococcal Sequencing Consortium; Reino UnidoFil: Kiran, Anmol. The Global Pneumococcal Sequencing Consortium; Reino UnidoFil: Skoczynska, Anna. The Global Pneumococcal Sequencing Consortium; Reino UnidoFil: Moiane, Benild. The Global Pneumococcal Sequencing Consortium; Reino UnidoFil: Beall, Bernard. The Global Pneumococcal Sequencing Consortium; Reino UnidoFil: Sigauque, Betuel. The Global Pneumococcal Sequencing Consortium; Reino UnidoFil: Aanensen, David. The Global Pneumococcal Sequencing Consortium; Reino UnidoFil: Lehmann, Deborah. The Global Pneumococcal Sequencing Consortium; Reino UnidoFil: Faccone, Diego Francisco. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas. Área de Antimicrobianos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin